management of long-chain fatty acid oxidation disorder · dehydrogenase deficiency (vlcadd), a rare...

Management of Long-Chain Fatty Acid Oxidation Disorder:

Pharmacist, Provider, and Patient Perspectives

This educational activity is sponsored by Postgraduate Healthcare Education, LLC

and supported by an educational grant from Ultragenyx Pharmaceutical, Inc.

Moderator/Faculty

Richard J. Faris, PhD, MSc, RPhSenior Vice President, Head of Pharmacy

PANTHERx Rare, LLC

Dr. Faris is Senior Vice President and Head of Pharmacy for PANTHERx Rare Pharmacy. In this role, he is responsible for RxARECARE pharmacy operations, clinical and patient engagement services, program management, and implementation.PANTHERx Rare Pharmacy focuses on serving people living with rare and devastating conditions. Prior to joining PANTHERx, Dr. Faris was Vice President for Clinical Strategy and Services with DaVita Rx. He has also served as Accredo Specialty Pharmacy’s Vice President for Clinical Services and Health Outcomes Solutions, and Medco’s/ESI’s National Practice Leader for Rare and Specialty Therapeutic Resource Centers. He has held leadership positions in health systems, industry, and academia, including being the founding Director for the Center for Pharmaceutical Outcomes and Policy with The Johns Hopkins Hospital. Dr. Faris received his Pharmacy degree from the University of Mississippi and completed a combined Masters degree/residency program with the University of Minnesota and United and Children’s Hospitals of St. Paul. He went on to complete his PhD at the University of Florida. He has served on committees for several national organizations and was recently a Board Member for the Pharmacy Quality Alliance, where he also chaired specialty pharmacy measure development efforts for several years.

Faculty

Nicola Longo, MD, PhDProfessor of Pediatrics and Chief

Division of Medical Genetics, Department of Pediatrics

Medical Genetics/Pediatrics

University of Utah

Salt Lake City, UT

Dr. Longo is Professor of Pediatrics and Chief in the Division of Medical Genetics, Department of Pediatrics at the University of Utah in Salt Lake City. He received his MD and PhD in molecular biology and pathology from the University of Parma School of Medicine in Italy. He then trained in Pediatrics, Medical and Biochemical Genetics at Emory University in Atlanta, Georgia. Dr. Longo is board certified in medical genetics and clinical biochemical genetics. His research concerns the molecular bases of metabolic disorders, their natural history, their identification through newborn screening, and the development of novel therapies.

Faculty

Tasia Rechisky

Tasia Rechisky is a Boston University graduate and long-time rare disease advocate.

At six months of age, Tasia was diagnosed with Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD), a rare metabolic disorder. She is an active member of the broader rare disease community, speaking at several universities and forums to physicians, genetic counselors, medical students, and researchers on the impact of living with a rare disease and, specifically, a fatty acid oxidation disorder. She is a committee member of Rare New England and a member of the Fatty Acid Oxidation Disorder patient leadership council for Ultragenyx Pharmaceutical.

Disclosures

Dr. Faris has disclosed that he is an employee of PANTHERx Rare Pharmacy.

Dr. Longo has disclosed that he has served as a consultant and clinical investigator for ReneoPharmaceuticals and Ultragenyx Pharmaceutical, Inc.

Ms. Rechisky has disclosed that she has served as a consultant for the Ultragenyx Patient Leadership Council.

The clinical reviewer, Daphne Davis, PharmD, BCOP has no actual or potential conflicts of interest in relation to this program.

Susanne Batesko, RN, BSN, Kim Miniter, MSEd, and Susan R. Grady, MSN, RN-BC, as well as the planners, managers, and other individuals, not previously disclosed, who are in a position to control the content of Postgraduate Healthcare Education (PHE) continuing education activities hereby state that they have no relevant conflicts of interest and no financial relationships or relationships to products or devices during the past 12 months to disclose in relation to this activity. PHE is committed to providing participants with a quality learning experience and to improve clinical outcomes without promoting the financial interests of a proprietary business.

Postgraduate Healthcare Education, LLC is

accredited by the Accreditation Council for

Pharmacy Education as a provider of continuing

pharmacy education.

UAN: 0430-0000-20-013-H01-P

Credits: 1.5 hour (0.15 CEU)

Type of Activity: Application

Dr. Richard Faris

Learning Objectives

• Identify the signs and symptoms of long-chain fatty acid oxidation

disorder (LCFAOD)

• Design an appropriate diet for a patient with LCFAOD

• Describe current treatments for LCFAOD

• Explain the potential role of triheptanoin and other emerging

treatments for LCFAOD

• Describe the role of specialty pharmacy in rare diseases

Dr. Nicola Longo

• Define the role of fatty acid oxidation in fasting

• Recognize the role of carnitine in fatty acid oxidation

• Define principles of treatment of fatty acid oxidation defects

Learning Objectives

• Fatty acid oxidation plays a major role in energy production during fasting

• It requires at least 20 individual steps, some of which are catalyzed by enzymes with overlapping chain-length specificities

• Carnitine carries fatty acids inside mitochondria• The beta oxidation cycle can extract energy from them

• All known fatty acid oxidation defects are transmitted as autosomal recessive traits

Longo N, et al. Biochim Biophys Acta. 2016;1863(10):2422-35.

Fatty Acid Oxidation

ADIPOSE TISSUE

LIVER

FATTY ACIDS

KETONES

HEART

SKELETAL MUSCLE

FATTY ACID OXIDATIONDURING FASTING

ß-hydroxybutyrate

acetoacetate

BRAIN

Fatty Acid Oxidation

ADIPOSE TISSUE

LIVER

FATTY ACIDS

KETONES

HEART

SKELETAL

MUSCLE

DEFECTIVE FATTY ACID OXIDATION

X

STEATOSIS

CARDIOMYOPATHY

ARRHYTHMIA

MYOPATHY

HYPOTONIA

MYOGLOBINURIA

BRAIN

LOSS OF

CONSCIOUSNESS

• Most fatty acid oxidation defects are episodic and clinically silent when fat is not utilized

• Triggering conditions include fever, infections, gastroenteritis, and reduced caloric intake

• Children often present shortly after birth (initiation of breastfeeding) or at any age during an illness causing catabolism

Triggers of Fatty Acid Oxidation Defects

• Fatty acid oxidation disorders (FAODs) are relatively frequent

• Cause: More than 20 enzymes/transporters are involved in fatty acid oxidation

• They are all autosomal recessive

• Epidemiology: Most frequent is MCAD deficiency (1:10,000)• All others are much rarer (1:30,000-1:1,000,000)

• Pathogenesis: Accumulation of fat and toxic metabolites, lack of energy, cell death

• On autopsy, fat infiltration of all tissues is observed

Fatty Acid Oxidation Disorders

MCAD, medium-chain acyl-CoA dehydrogenase.

• Presentation: Fasting-induced hypoketotic hypoglycemia, liver failure, hyperammonemia (Reye syndrome), cardiomyopathy, myopathy, hypotonia, neuropathy, arrhythmia, sudden death, rhabdomyolysis

• Diagnosis: Plasma carnitine and acylcarnitine profile, urine organic acids during acute attack, free fatty acids, DNA studies, in vitro probes, fibroblast enzyme/transport assay

• Therapy: Fasting avoidance, prompt treatment of infections, low-fat diet, MCT oil/triheptanoin (in some), carnitine, essential fatty acids, ketones


MCT, medium-chain triglyceride.

Longo N, et al. Am J Med Genet C

Semin Med Genet. 2006;142(2):77-85.

Fatty acids are

conjugated with

carnitine to

enter the

mitochondrial

matrix

Carnitine in Fatty Acid Oxidation

-OXIDATION

Acyl-CoA dehydrogenases

Acyl-CoA

2,3-Enoyl-CoA

FAD

FADH2

Hydratases H2O

L-3-hydroxyacyl-CoANAD

NADH2Hydroxyacyl-CoA dehydrogenases

3-Ketoacyl-CoA

HSCoAThiolases

Acyl-CoA

(n-2)

Recycles

+ Acetyl-CoA

Ketogenesis

liver

muscleTCA cycle

VLCAD: C14-C20

LCAD: C12-C18

MCAD: C4-C12

SCAD: C4-C6

LCHAD (TFP): C12-C18

SCHAD: C4>C16

TFP C6-C16

MKAT C4-C12

ketothiolase C4

C16:0 palmitoylCoA

O

SCoA

O

SCoA

O

SCoA

OH

O

SCoA

O

O

SCoAC14:0 myristoyl-CoA

O

SCoA

TFP C12-C18

Crotonase C4>C14

Beta oxidation

shortens long-chain

fatty acids by 2

carbons at a time,

generating energy

through the Krebs

cycle or ketones in

the liver

Pasquali M, Longo N. Newborn Screening and Inborn

Errors of Metabolism. Chapter 70. In: Burtis CA,

Ashwood ER, Bruns DE, eds. Tietz Textbook of Clinical

Chemistry and Molecular Diagnostics. 6th ed. St. Louis:

Saunders, 2017.

Mitochondrial Fatty Acid Oxidation

• Pathogenesis: Accumulation of fat and toxic metabolites• Lack of energy

• Long-chain fatty acids and, to a lesser extent, long-chain acylcarnitines, can have toxic effects and cause cardiac arrhythmia

• Lack of energy can lead to organ failure and cell death• Hypoglycemia can be present but is usually a late sign of FAODs

Pasquali M, Longo N. Newborn Screening and Inborn Errors of Metabolism. Chapter 70. In: Burtis CA, Ashwood ER,

Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. St. Louis: Saunders, 2017.


Emergency Protocol for Patients with FAOD

• If unable to eat, give IV fluids to provide calories: • D10 (10% glucose); 75-150 mEq/L NaCl; 20 mEq/L KCl at 150 mL/kg

per day

• Labs/imaging to identify cause of problems, mostly infections (cultures/X-rays)

• Electrolytes, liver function tests, creatinine kinase, plasma ammonia, urine analysis

• Start enteral feeds as soon as tolerated

IV, intravenous.

Medium-Chain Fats in the Therapy of

LCFAODs

• Clinical complications caused by energy

deficiency resulting from insufficient

availability of intermediates of the citric acid

cycle that compromises ATP production

• With even-chain fatty acids (MCT oil),

substrate is provided (acetyl-CoA), but

intermediates of the Krebs cycle might run

out

• Triheptanoin replenishes succinyl-CoA

(anaplerosis) while also providing acetyl-

CoA

Roe CR, Brunengraber H. Mol Genet Metab. 2015;116(4):260-8.

3y

I

III

3d

II31 y 25 y

2d

Neonatal Cardiac Arrest

• Term infant developed hypothermia, desaturations, low blood pressure, and hypoglycemia (glucose 7 mg/dL) at 18 h of age

• Intubated, developed tachy- and bradycardia

• Cardiac ECHO: cardiomyopathy

• Had cardiac arrest requiring 5 min of chest compressions

• Had mild hyperammonemia with increased liver function tests (ALT/AST up to 400) and mildly increased CPK (up to 350)

• Started on IV glucose with stabilization

ALT, alanine transaminase;

AST, aspartate transaminase;

CPK, creatine phosphokinase;

ECHO, echocardiogram.

Diagnosis: Plasma Acylcarnitine Profile

Carnitine Acylcarnitine Translocase (CACT) Deficiency MIM 212138

• Frequency: Very rare

• Cause/Pathogenesis: Deficiency of the acylcarnitine translocator impairs entry of long-chain acylcarnitines into mitochondria

• Results in the accumulation of long-chain acylcarnitine, long-chain fatty acids, and defective energy production

• Presentation: Arrhythmia, cardiac arrest shortly after birth, hypoketotic hypoglycemia, cardiomyopathy

• Diagnosis: Abnormal acylcarnitine profile (low C0, increased C16-C18:1), abnormal organic acids (dicarboxylic aciduria)

• Confirmed by DNA testing

• Identified by newborn screening• Most infants present before newborn screening is obtained

Iacobazzi V, et al. Am J Med

Genet A. 2004;126A(2):150-5.

Carnitine Acylcarnitine Translocase (CACT) Deficiency MIM 212138

• Therapy: Fasting avoidance, low-fat diet, MCT oil, carnitine

• Monitoring: Acylcarnitine profile, carnitine F & T, CK, ALT, AST

• Prognosis: Not always good, but there are teenagers with milder variants doing well with therapy

Iacobazzi V, et al. Am J Med Genet A. 2004;126A(2):150-5.

CK, creatine kinase.

Longo et al (2006)

Am J Med Genet, in press

The Carnitine Cycle in Fatty Acid Oxidation

Longo N, et al. Am J Med Genet C

Semin Med Genet. 2006;142(2):77-85.

Age (months)0 1 2 3 4 5 6

Ac

ylc

arn

itin

e (

M)

0

2

4

6 C16

C18:1

C18:2

C16:1

Ca

rnit

ine

(

M)

0

10

20

30

40

50

Free

Acetyl (C2)

A

B

1 2 3 4 5 6inner mitochondrial

membrane

cytoplasm

matrix

{ { {100 AA 100 AA 100 AA

Q238R

Iacobazzi V, et al. Am J Med Genet A. 2004;126A(2):150-5.

C

AC

T A

CT

IVIT

Yacety

lcarn

itin

e f

orm

ati

on

(m

g/h

)

0

20

40C

ON

TR

OL

S

AF

FE

CT

ED

PA

TIE

NT

Progressive Normalization of Carnitine Levels in a Patient with CACT Deficiency with Carnitine and Medium-Chain Triglycerides

Carnitine Palmitoyl Transferase-2 (CPT-2) Deficiency

• 78-year-old man hospitalized for persistent muscle cramps and myoglobinuria

• Has not been able to run or participate in sustained physical exercise since he was a teenager

• Was in the military during 2 wars but was assigned to an office

• Now, he develops muscle pain and myoglobinuria even without exercise (P50H/unk)

CPT-2 Deficiency

• Frequency: Very rare• Myopathic form is still rare, but with several reported cases (> 300)

• Cause/Pathogenesis: Deficiency of CPT-2 impairs the transfer of long-chain fatty acids from carnitine to CoA synthesis of long-chain acylcarnitine

• Results in the accumulation of long-chain acylcarnitine, long-chain fatty acids, and defective energy production

• Presentation: 1. Lethal neonatal 608836: respiratory failure, liver failure, cardiomyopathy,

arrhythmia, hypoglycemia

2. Severe infantile 600649: hypoglycemia, seizures, hepatomegaly, cardiomyopathy, arrhythmia

3. Myopathic 255110: muscle pain with exercise


Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. St. Louis: Saunders; 2017.

CPT-2 Deficiency

• Diagnosis: Abnormal acylcarnitine profile (increased C16-C18)• Confirmed by DNA testing

• Identified by newborn screening, but infants can be easily missed (profile can be normal at birth)

• Therapy: Fasting avoidance, MCT oil, sugary drinks with exercise

• Monitoring: ALT, AST, CK, acylcarnitines

• Prognosis: Myopathic form is compatible with long life


Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. St. Louis: Saunders; 2017.

Rovelli V, et al. Mol Genet Metab. 2019;127(1):64-73.

Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency MIM 201450

• 8-year-old hospitalized after being unable to move or wake up completely

• Woke up moaning, crying, unable to focus, drink, or walk

• Admitted to Intensive Care for 6 days and found to have cardiomyopathy with low cardiac ejection fraction, elevated CK, and cardiomegaly on chest X-ray

VLCAD Deficiency MIM 201450

• Relatively common FAOD

• Frequency: 1:63,481 (USA), 1:27,617 (Utah)

• Cause: Mutations in ACADVL gene

• Presentation:1. Early onset, hypertrophic cardiomyopathy, high morbidity and mortality

2. Milder form with hypoketotic hypoglycemia, similar to MCAD deficiency with

increased LFTs, elevated CPK

3. Stress-induced rhabdomyolysis, like myopathic CPT2 deficiency


LFTs, liver function tests.

VLCAD Deficiency MIM 201450

• Diagnosis: Plasma acylcarnitine profile (elevated C14:1, normalizes rapidly

after stress), DNA testing (part of initial tests), fatty acid oxidation fluxes,

VLCAD enzyme assay

• Therapy: Fasting avoidance, prompt treatment of infection, MCT oil in

patients with persistently abnormal acylcarnitines, low-fat diet, essential

fatty acids, carnitine (25 mg/kg) with low plasma levels (unproven), MCT

oil/triheptanoin, sugary drinks with exercise

• Monitoring: AST, ALT, CK, carnitine F & T, acylcarnitines, cardiac ECHO,

ECG, Holter monitoring

• Prognosis: Can be good with treatment


ECG, electrocardiogram.

Long-Chain 3-OH-Acyl-CoA Dehydrogenase (LCHAD) 609016 / Trifunctional Protein (TFP) 609105 Deficiency

• LCHAD is part of a trifunctional protein (TFP)• Mutations can abolish all 3 functions or only LCHAD activity

• Frequency: 1:303,222 (USA), 1:255,365 (Utah)

• Cause: Mutations in HADHA or HADHB gene

• Presentation: IUGR, prematurity, fasting-induced vomiting and

hypoglycemia, hypotonia, cardiomyopathy, liver dysfunction, sudden

death• Rhabdomyolysis with stress/exercise/fasting

• Retinitis pigmentosa with time

• Neuropathy (more pronounced in TFP deficiency)

• Preeclampsia in mothers of infants with LCHAD deficiency

Longo N, et al. Am J Med Genet C Semin Med Genet. 2006;142(2):77-85.

IUGR, intrauterine growth restriction.

• Diagnosis: Plasma acylcarnitine profile, DNA testing

• Therapy: Fasting avoidance, MCT oil/triheptanoin, low-fat diet,

essential fatty acids, carnitine (25 mg/kg) with low plasma levels

(unproven)

• Monitoring: AST, ALT, CK, carnitine F & T, acylcarnitines, essential

fatty acids, eye examination, cardiac ECHO, ECG, Holter monitoring

• Prognosis: Bad without treatment• Even with treatment, there are problems (muscle pain, retinitis pigmentosa,

neuropathy)

Long-Chain 3-OH-Acyl-CoA Dehydrogenase (LCHAD) 609016 / Trifunctional Protein (TFP) 609105 Deficiency

Longo N, et al. Am J Med Genet C Semin Med Genet. 2006;142(2):77-85.

-OXIDATION

Acyl-CoA dehydrogenases

Acyl-CoA

2,3-Enoyl-CoA

FAD

FADH2

Hydratases H2O

L-3-hydroxyacyl-CoANAD

NADH2Hydroxyacyl-CoA dehydrogenases

3-Ketoacyl-CoA

HSCoAThiolases

Acyl-CoA

(n-2)

Recycles

+ Acetyl-CoA

Ketogenesis

liver

muscleTCA cycle

VLCAD: C14-C20

LCAD: C12-C18

MCAD: C4-C12

SCAD: C4-C6

LCHAD (TFP): C12-C18

SCHAD: C4>C16

TFP C6-C16

MKAT C4-C12

ketothiolase C4

C16:0 palmitoylCoA

O

SCoA

O

SCoA

O

SCoA

OH

O

SCoA

O

O

SCoAC14:0 myristoyl-CoA

O

SCoA

TFP C12-C18

Crotonase C4>C14

Pasquali M, Longo N. Newborn

Screening and Inborn Errors of

Metabolism. Chapter 70. In:

Burtis CA, Ashwood ER, Bruns

DE, eds. Tietz Textbook of

Clinical Chemistry and Molecular

Diagnostics. 6th ed. St. Louis:

Saunders, 2017.

LCHAD Deficiency

• AFLP (acute fatty liver of pregnancy) syndrome or HELLP (hypertension, elevated liver functions, and low platelets) are frequent in mothers carrying a fetus with LCHAD deficiency

• Patients do very well when treated but can decompensate with fever, acquire infections, and require prompt hospital admission to receive IV glucose

• Mentality is normal

De Biase I, et al. JIMD Rep. 2017;31:63-71.

LCHAD Deficiency

• Oxidation of fatty acids plays an important role in energy production during fasting

• Inherited defects of the carnitine cycle and fatty acid oxidation are relatively frequent and can present at any age when energy from fat is needed (fasting, infections, fever)

• Patients can appear perfectly normal between episodes• DNA testing is usually necessary to confirm or exclude the diagnosis

Summary

• LCFAODs include CACT, CPT2, VLCAD, and LCHAD/TFP deficiency

• Diagnosis: Plasma acylcarnitine profile can pinpoint the specific defect

• Confirmation is by DNA testing

• Therapy in LCFAODs requires fasting avoidance, exercise limitation, and administration of medium-chain fatty acids or triheptanoin while restricting long-chain fats in the diet

Summary

Tasia’s Story:Living with FAOD

Diagnosis

• Normal pregnancy and delivery

• Noticed symptoms such as

lethargy, breast milk

intolerance, projectile vomiting

• Metabolic crisis at 4 months• Coma

• ECHO showed heart

enlargement (5X)

• Originally diagnosed with

LCHAD and then further

testing confirmed VLCADD

Infancy

• Nose tube for 6 months

• Occupational therapy to transition to oral feeding

• Formula (MCT oil + Polycose)

• Caretaker: RN trained

Childhood

• Attended pre-school and then public

school• 504 plan

• Symptoms limited• Experienced some low blood sugar

• Muscle pain rarely

• Low-fat diet

• Active but took precautions• Carried snacks

• Stayed hydrated

• Strict medication regimen

• Monitored physical activity closely

Adolescence

• Puberty (age 11) triggered symptoms

• Muscle pain and rhabdomyolysis

• Constant fatigue

• Physical activity became limited

• Frequent hospitalization

• Depression and social isolation

• Started C7 (triheptanoin) trial at age 15

• By late adolescence, quality of life much improved

Young Adulthood

• 4 years of college at Boston University

• Learning to better manage the disease on

my own

• Hospitalized 2-3 times per year in first 2

years, down to once per year or less by

end of college

• Switched care teams from children’s

hospital to adult hospital to make hospital

admission and care coordination easier

Living with FAOD: Common Triggers

• Viral illness, infection, allergies, injury

• Overexertion

• Lack of sleep

• Extreme heat or cold

• Fasting or not enough calorie intake

• Missed doses of medication

• Stress

• Menstrual cycle

Living with FAOD: Keys to Successful Management

• Diligence about medication and diet

• Routine

• Listen to my body

• Hydration

• Reduce stress

• Stay active and build muscle during healthy times

• Manage secondary conditions that may be a trigger (e.g., blood pressure, migraines)

• Build a support system

• Community

Pharmacist’s Role

Specialty Pharmacy: Learning Objectives

• Describe the role of specialty pharmacy in rare diseases

• Identify therapies coming to market as specialty products

• Understand disease state and product profiles

• Impact patient care through services

ARS #1

1. According to the Orphan Drug Act (amended in 1984), no more than how many patients can be affected in the United States for a disease to be considered “Rare”?

A. 7,000

B. 50,000

C. 100,000

D. 200,000

E. 500,000

What is a Rare Disease?

• Estimated 7,000 rare diseases• Only 5% have treatments

• U.S.: Orphan Drug Act (1983, amended 1984)• Disease that affects less than 200,000 people in the U.S.

• 7 years of market exclusivity

• Tax credits for costs incurred in evaluation

• EU NICE: Ultra Rare - 1:50,000• Approximately 6,500 patients in the U.S.

• Manufacturer focus

• Role for Specialty Pharmacy

Specialty Pharmacy and FAOD

• New products to market likely to be specialty

• Multiple disorders under FAOD

• Product profiles

• Patient needs

Where Do We Start?

• Understanding of the disease state(s)• Causes

• Impact on lives

• Current treatments

• Understanding the therapies• Product profiles

• Needs for safe and effective dispensing

• Understanding the patient• Their journey to get here

• Patient education and assistance

• Program design

Therapy Considerations

• Route of administration and dosage form• Oral

• Solution

• Special handling requirements

• Educational opportunities• How to use therapy properly

• Storage and handling

• Potential adverse effects and mitigation strategies

• Adherence and persistence

Understanding the Patient

• Each has their own story• How did they get here?

• What was their journey?

• They have unique needs and desires• How do they want to communicate?

• Do they have any caregivers?

• How can we make their life easier?

Specialty Pharmacy

• Reimbursement services• BI/BV

• Co-pay support program knowledge

• Patient assistance programs

• Understanding of foundations for specific diseases

• PA understanding/support

• Care management• Onboarding

• Initial fill

• Refill services

• Off-cycle contact

• Data and reporting• Insights

• Regular reportingBI/BV, benefit identification/benefit verification; PA, prior authorization.

Dietary Assistance

Questions & Answers

Thank you!

management of long-chain fatty acid oxidation disorder · dehydrogenase deficiency (vlcadd), a rare...

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